Bendavia Trial Shows No Benefit in Angioplasty

Researchers had high hopes for the potential tissue-damage mediation capabilities of Bendavia, an experimental drug that targets the mitochondria. But a trial of Bendavia in patients undergoing angioplasty failed to show any significant benefit.

Cardiology researchers had high hopes for the potential tissue-damage mediation capabilities of Bendavia (Stealth Biotherapeutics), an experimental drug that targets the mitochondria.

The drug is in clinical trials for a number of uses, including in heart failure, kidney disease, metabolic disease, and neurodegenerative disease.

The expectation in a trial of Bendavia in preventing reperfusion injury following angioplasty or stent placement was that the drug would prevent damage to heart tissue by boosting heart cells’ energy production, a job that falls to the mitochondria, the cellular power plant.

But at the 2015 American College of Cardiology annual meeting in San Diego, CA, a Harvard team reported that Bendavia did not work well in preventing such scarring.

“It did not reduce infarct sizes,” said C. Michael Gibson, MD, professor of medicine at Harvard Medical School and the study’s lead author, though Bendavia did show potential benefit in reducing kidney damage associated with such patients.

The results in animal studies had been promising, Gibson noted, but were not born out in use in humans.

The study was the first randomized, controlled trial of Bendavia in angioplasty patients.

Patients who got the drug showed a 10% reduction in scarring during the first 3 days after surgery,but the difference was not statistically significant. (The tissue damage was measured by tracking the patients’ levels of creatinine kinase-MB.)

Among possible reasons for the disappointing results is that size of the group of patients in the trial (300) was about half what the original enrollment plan called for.

That was because a surprising number of patients who were candidates for artery-clearing interventions had culprit arteries that were partially open, not closed as the study criteria required, Gibson said.

Another factor was that many patients had hypertension, a condition that results in thicker heart walls and could have interfered with the drug’s potential to be effective.

The fact that it also showed a reduced i ncidence of new onset heart failure in the first 8 hours after the infusion of the drug could also indicate it could help improve heart puping function for heart failure patient, he said.

Still, the potential of Bendavia to reduce kidney damage bears further study.

“That’s what you do in a Phase II trial,” Gibson said, “you explore.”

Commenting on the presentation, Eric Peterson, MD said he believes “this drug’s story is not yet written; stay tuned.”